Analytical and Bioanalytical Chemistry

, Volume 407, Issue 8, pp 2107–2116 | Cite as

Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI

  • Achim Buck
  • Susanne Halbritter
  • Christoph Späth
  • Annette Feuchtinger
  • Michaela Aichler
  • Horst Zitzelsberger
  • Klaus-Peter Janssen
  • Axel WalchEmail author
Research Paper
Part of the following topical collections:
  1. Mass Spectrometry Imaging


Tissue distribution and quantitative analysis of small molecules is a key to assess the mechanism of drug action and evaluate treatment efficacy. The prodrug irinotecan (CPT-11) is widely used for chemotherapeutic treatment of colorectal cancer. CPT-11 requires conversion into its active metabolite SN-38 to exert the desired pharmacological effect. MALDI-Fourier transform ion cyclotron resonance (FT-ICR) and MALDI-time-of-flight (TOF) mass spectrometry imaging (MSI) were performed for detection of CPT-11 and SN-38 in tissue sections from mice post CPT-11 injection. In-depth information was gained about the distribution and quantity of drug compounds in normal and tumor tissue. The prodrug was metabolized, as proven by the detection of SN-38 in liver, kidney and digestive tract. In tumors from genetic mouse models for colorectal cancer (Apc 1638N/wt x pvillin-Kras V12G ), CPT-11 was detected but not the active metabolite. In order to correlate drug distribution relative to vascularization, MALDI data were superimposed with CD31 (PECAM-1) immunohistochemistry. This analysis indicated that intratumoral access of CPT-11 mainly occurred by extravasation from microvessels. The present study exploits the power of MALDI MSI in drug analysis, and presents a novel approach to monitor drug distribution in relation to vessel functionality in preclinical and clinical research.


Mass spectrometry MALDI imaging Drug monitoring/drug screening Irinotecan SN-38 



This work was supported by Ministry of Education and Research of the Federal Republic of Germany BMBF (No. 01ZX1310B and No. 01IB10004E), the Deutsche Forschungsgemeinschaft (SFB 824 TP Z2 and WA 1656/3-1, HO 1258/3-1), and Helmholtz Zentrum München (TKP-Project). The authors thank Ulrike Buchholz, Claudia-Mareike Pflüger, Gabriele Mettenleiter, and Andreas Voss for their excellent technical assistance.

Supplementary material

216_2014_8237_MOESM1_ESM.pdf (177 kb)
ESM 1 (PDF 176 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Achim Buck
    • 1
  • Susanne Halbritter
    • 1
  • Christoph Späth
    • 3
  • Annette Feuchtinger
    • 1
  • Michaela Aichler
    • 1
  • Horst Zitzelsberger
    • 2
  • Klaus-Peter Janssen
    • 3
  • Axel Walch
    • 1
    Email author
  1. 1.Research Unit Analytical Pathology, Institute of Pathology, Helmholtz Zentrum MünchenGerman Research Center for Environmental HealthNeuherbergGermany
  2. 2.Research Unit Radiation Cytogenetics, Helmholtz Zentrum MünchenGerman Research Center for Environmental HealthNeuherbergGermany
  3. 3.Department of Surgery, Klinikum rechts der IsarTechnische Universität MünchenMunichGermany

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